职务：研究员/硕士生导师/所长

学历：博士

电子邮件： bixingzhao@gmail.com

主要研究方向：肿瘤相关细胞信号转导通路、免疫治疗与精准医学方面的基础与临床转化研究

教育工作经历：

1999/09 - 2003/07，厦门大学，生物科学， 本科

2003/09 - 2006/07，厦门大学，细胞生物学，硕士

2006/09 - 2011/04，厦门大学，细胞生物学，博士

2011/04 - 2014/12，厦门大学附属中山医院，博士后

2014/08 - 2014/11，美国德克萨斯州立大学圣安东尼奥健康科学中心，访问学者

2015/01 - 至今，福建医科大学孟超肝胆医院，副研究员，研究员

2017/09 – 2022/12，福建医科大学孟超肝胆医院肝病研究所，副所长

2017/06 - 至今，3522vip浦京集团官网孟超医学与交叉科学中心，副教授、硕士生导师

2022/12 – 至今，福建医科大学孟超肝胆医院肝病研究所，所长

教学简介：

参与承担本科生课程《肿瘤生物学》教学。

科研简介：主要从事肿瘤相关细胞信号转导通路、免疫治疗与精准医学方面的基础与临床转化研究。主持国家自然科学基金面上项目、科技部重点专项等多项国家级和省市级研究课题。在The EMBO Journal, Signal Transduction and Targeted Therapy, Theranostics等国际知名期刊上发表SCI收录论文四十多篇。入选福建省第二批“雏鹰计划”青年拔尖人才，福建省百千万人才工程省级人选，福建省高层次人才（C类）；曾获得福建省科技进步一等奖、福建省自然科学一等奖、厦门市科学技术进步一等奖、福州市青年科技奖、福建医学科技奖、福建省抗癌协会科技进步一等奖等荣誉。

社会兼职：福建省医学会肝病学分会青年委员会副主任委员、中国抗癌协会抗癌药物专业委员会委员、中国医师协会中西医结合医师分会基础与转化医学专业委员会委员、中国医药生物技术协会科研实验室建设与管理分会委员、福建省药理学会肿瘤药理专业委员会常委、中华医学会肝病学分会肝病基础医学与实验诊断协作组成员、福建省医学会外科学分会实验外科及转化医学学组委员。

科研项目：

1. 福建省科技创新联合资金项目（2021Y9032），环状RNA肿瘤新抗原疫苗在肿瘤免疫治疗中的应用研究，2022/10-2025/10，100万，主持。

2. 福建省中央引导地方科技发展资金项目（2022L3030），肝癌免疫逃逸相关lncRNA调控网络研究(福建省肝胆胰肿瘤临床医学研究中心)，2022/08-2025/08，40万，主持。

3. 福建省卫生教育联合攻关计划项目（2019-WJ-19），长链非编码RNA FAM99A在缺氧诱导的肝癌转移中的作用及机制研究，2019/09-2022/09，20万，主持。

4. 福建省卫生健康中青年骨干人才培养项目（2020GGA072），METTL16通过调控LncRNA AC079360.1 m6A甲基化促进肝癌侵袭转移，2021/01-2023/12，10万，主持。

5. 福州市卫生健康系统科技计划创新团队培育项目（2021-S-wt2），长链非编码RNA Lnc-PLA2G4A-4通过miR-23b/Versican信号轴调控肝癌的侵袭转移，2021/09-2024/09，8万，主持。

6. 国家自然科学基金面上项目（81672376），SALL4及其相互作用蛋白对肝癌治疗抗性的调控功能研究，2017/01-2020/12，57万，主持。

7. 国家重点研发计划“科技助力经济2020”重点专项（SQ2020YFF0426513），病毒性肝炎相关肝癌人群预警和早筛试剂研发，2020/07-2022/6，100万，合作主持。

8. 福州市卫生计生系统科技计划创新团队培育项目(2017-S-wt2)，Ku80通过SALL4调控肝癌细胞干性，2017/08-2020/07，8万，主持。

9. 福建省医学创新课题（2016-CX-48） SALL4在肝癌细胞DNA损伤修复中的作用研究，2016/10-2019/09，12万，主持。

10. 福建省自然科学基金面上项目（2016J01417），10-23 型脱氧核酶靶向SALL4 抑制肝癌细胞侵袭转移的实验研究，2016/04-2019/04，5万，主持。

11. 福州市科技计划项目（2015-S-143-19），靶向SALL4基因的microRNA对人肝癌细胞恶性表型的影响，2015/04-2018/03，3万，主持。

12. 国家自然科学基金青年项目（81302069），Cx32通过p53信号通路调控肝癌细胞侵袭转移，2014/01-2016/12，24万，主持。

13. 中国博士后科学基金面上项目（2013M531550），CX32通过p53和Akt信号通路调控肝癌细胞增殖与侵袭转移，2013/01-2015/01，5万，主持。

14. 福建省自然科学基金青年创新项目（2012D055），细胞连接蛋白connexin32在肝癌发生发展中的作用研究，2012/07-2013/11，4万，主持。

已发表论文：（*为通讯作者）

(1) Lin Y, Wang F, Zhong Y, Cheng NM, Xiong J, Zheng X, Zhou Y, Gao S, Li F, Wang Y, Yang X, Zhao B*. Long non-coding RNA COX7C-5 promotes hepatocellular carcinoma progression via miR-581/ZEB2 axis. Cellular Signalling. 2023; 101: 110501.

(2) You S, Luo Z, Cheng N, Wu M, Lai Y, Wang F, Zheng X, Wang Y, Liu X, Liu J, Zhao B*. Magnetically responsive nanoplatform targeting circRNA circ_0058051 inhibits hepatocellular carcinoma progression. Drug Delivery and Translational Research. 2023;13:782-794

(3) Bixing Zhao#, Kun Ke#, Yingchao Wang#, Fei Wang#, Yingjun Shi, Xiaoyuan Zheng, Xiaoyu Yang, Xiaolong Liu*, Jingfeng Liu*, HIF-1α and HDAC1 mediated regulation of FAM99A-miR92a signaling contributes to hypoxia induced HCC metastasis. Signal Transduction and Targeted Therapy. 2020; 5:118

(4) Liu J, Wang F, Zhang Y, Liu J, Zhao B*. ADAR1-Mediated RNA Editing and Its Role in Cancer. Front Cell Dev Biol. 2022;10:956649

(5) Ying Sun#, Xiaoyuan Zheng#, Hui Yuan, Geng Chen, Jiahe Ouyang, Jingfeng Liu, Xiaolong Liu, Xiaohua Xing*, Bixing Zhao*, Proteomic Analyses Reveal Divergent Ubiquitylation Patterns in Hepatocellula Carcinoma Cell Lines With Different Metastasis Potential. Journal of proteomics. 2020;225:103834.

(6) Bixing Zhao#, Yingchao Wang#, Xionghong Tan, Kun Ke, Cuilin Zhang, Yunzhen Gao, Naishun Liao, Yuan Dang, Yingjun Shi, Youshi Zheng, Xiaolong Liu*, Jingfeng Liu*, An optogenetic controllable T cell system for hepatocellular carcinoma immunotherapy. Theranostics. 2019; 9(7): 1837-1850.

(7) Bixing Zhao; Yingchao Wang; Xionghong Tan; Kun Ke; Xiaoyuan Zheng; Fei Wang; Shubing Lan; Naishun Liao; Zhixiong Cai; Yingjun Shi; Youshi Zheng; Yongping Lai; Lili Wang; Qin Li; Jingfeng Liu; Aimin Huang*; Xiaolong Liu*; Inflammatory Micro-environment Contributes to Stemness Properties and Metastatic Potential of HCC via the NF-kappaB/miR-497/SALL4 Axis. Molecular therapy oncolytics. 2019; 15, 79-90

(8) Bixing Zhao#, Xiaoyuan Zheng#, Xionghong Tan, Kun Ke, Fei Wang, YingchaoWang, Xiaohua Xing, Cuilin Zhang, Ping Hu, Shubing Lan, Qin Li, Aimin Huang*,  Xiaolong Liu*. Ku80 negatively regulates the expression of OCT4 via competitive binding to SALL4 and promoting lysosomal degradation of OCT4. The International Journal of Biochemistry & Cell Biology. 2020,118: 105664.

(9) Xing X, Yuan H, Sun Y, Ke K, Dong X, Chen H, Liu X, Zhao B*, Huang A*. ANXA2Tyr23 and FLNASer2152 phosphorylation associate with poor prognosis in hepatic carcinoma revealed by quantitative phosphoproteomics analysis. Journal of proteomics. 2019, 200:111-122.

(10) Hongzhi Liu#, Hui Chen#, Xiaomo Wu, Ying Sun, Yingchao Wang, Yongyi Zeng , Geng Chen, Xiaolong Liu, Xiaohua Xing*, Bixing Zhao*, Jingfeng Liu, The serum proteomics tracking of hepatocellular carcinoma early recurrence following radical resection. Cancer Management and Research. 2019;11: 2935-2946

(11) Shubing Lan, Xiaoyuan Zheng, Ping Hu, Xiaohua Xing, Kun Ke, Fei Wang, Niangmei Cheng, Qiuyu Zhuang, Xiaolong Liu, Jingfeng Liu, Bixing Zhao*, Yingchao Wang*. Moesin facilitates metastasis of Hepatocellular carcinoma cells by improving invadopodia formation and activating β-catenin/MMP9 axis. Biochemical and Biophysical Research Communications. 2020; 524(4):861-868.

(12) Youshi Zheng#, Naishun Liao#, Yuan Wu, Ju Gao, Zhenli Li, Wenwen Liu, Yingchao Wang, Ming Li, Xiaolou Li, Li Chen, Wenmin Zhang*, Bixing Zhao*, High expression of B7H2 or B7H3 is associated with poor prognosis in hepatocellular carcinoma, Molecular Medicine Reports. 2019; 19: 4315-4325.

(13) B. Zhao, W. Zhao, Y. Wang, Y. Xu, J. Xu, K. Tang, S. Zhang, Z. Yin, Q. Wu, and X. Wang*, Connexin32 regulates hepatoma cell metastasis and proliferation via the p53 and Akt pathways. Oncotarget, 2015. 6(12): p. 10116-33.

(14) B. Zhao, H. Chen, X. Du, J. Luo, J. He, R. Wang, Y. Wang, R. Wu, R. Hou, M. Hong, and Q. Wu*, Orphan receptor TR3 enhances p53 transactivation and represses DNA double-strand break repair in hepatoma cells under ionizing radiation. Molecular Endocrinology, 2011. 25(8): 1337-50.

(15) B. Zhao, H. Chen, N. Lei, G. Li, W. Zhao, Y. Zhan, B. Liu, S. Lin, and Q. Wu*, p53 mediates the negative regulation of MDM2 by orphan receptor TR3. The EMBO journal, 2006. 25(24): 5703-15.

(16) X.Lin^#, B. Zhao^#, H. Chen, X. Ye, C. Yang, H. Zhou, M. Zhang, S. Lin, and Q. Wu, RXRalpha acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells. J Cell Sci, 2004. 117(Pt 23):5609-21.

(17) 邢晓华，袁晖，赵必星*. NEDD8抑制剂MLN4924抑制肝细胞癌恶性表型的研究.山西医科大学学报,2021,52:123-128.

(18) 王珊,王菲,郑晓源,赵必星*. 靶向SALL4脱氧核酶抑制肝细胞癌恶性表型的实验研究.山西医科大学学报,2019(11):1499-1504.

(19) 赖永平,曾金华,谭雄红,柯坤,赵必星*,成簇规律间隔的短回文重复序列及其相关蛋白9敲除Ku80基因提高HEK293T细胞对阿霉素的敏感性, 中华实验外科杂志, 2018, 35(8): 1437-1440.

(20) Liao N, Su L, Zheng Y, Zhao B, Wu M, Zhang D, Yang H, Liu X, Song J. In Vivo Tracking of Cell Viability for Adoptive Natural Killer Cell-Based Immunotherapy by Ratiometric NIR-II Fluorescence Imaging. Angew Chem Int Ed Engl. 2021;60(38):20888-20896.

(21) Liu H, Lin S, Ao X, Gong X, Liu C, Xu D, Huang Y, Liu Z, Zhao B, Liu X, Han X, Ye H. Meta-analysis of transcriptome datasets: An alternative method to study IL-6 regulation in coronavirus disease 2019. Comput Struct Biotechnol J. 2021;19:767-776.

(22) Xing X, Yuan H, Liu H, Tan X, Zhao B, Wang Y, Ouyang J, Lin M, Liu X, Huang A. Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase II in Hepatocellular Carcinoma. Genomics Proteomics Bioinformatics. 2021;19(1):94-107.

(23) Zhong Y, Yang Y, He L, Zhou Y, Cheng N, Chen G, Zhao B, Wang Y, Wang G, Liu X. Development of Prognostic Evaluation Model to Predict the Overall Survival and Early Recurrence of Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021;8:301-312.

(24) Qiao S, Xin F, Wu M, Zheng Y, Zhao B, Zhang C, Liu X, Wei Z, Liu J. A remotely controlled NIR-II photothermal-sensitive transgene system for hepatocellular carcinoma synergistic therapy. J Mater Chem B. 2021;9(25):5083-5091.

(25) Xiaohua Xing, Hui Yuan, Ying Sun, Kun Ke, Xiuqing Dong, Hui Chen, Xiaolong Liu, Bixing Zhao, Aimin Huang. Dataset for quantitative phospho-proteomics analysis of a serial hepatoma cell lines with increasing invasion and metastasis potential. Data in Brief, 2019; 27:104634.

(26) Naishun Liao, Yingjun Shi, Yingchao Wang, Fangyu Liao, Bixing Zhao, Youshi Zheng, Yongyi Zeng, Xiaolong Liu, Jingfeng Liu. Antioxidant preconditioning improves therapeutic outcomes of adipose tissue-derived mesenchymal stem cells through enhancing intrahepatic engraftment efficiency in a mouse liver fibrosis model. Stem Cell Res Ther. 2020;11(1):237.

(27) Lin X, Huang Y, Sun Y, Tan X, Ouyang J, Zhao B, Wang Y, Xing X, Liu J. 4E-BP1Thr46 Phosphorylation Association with Poor Prognosis in Quantitative Phosphoproteomics of Portal Vein Tumor Thrombus Revealed that 4E-BP1Thr46 Phosphorylation is Associated with Poor Prognosis in HCC. Cancer Management and Research, 2020, 12: 103-115.

(28) Liuping Luo, Lihong Chen, Kun Ke, Bixing Zhao, Lili Wang, Cuilin Zhang, Fei Wang, Naishun Liao, Xiaoyuan Zheng, Xiaolong Liu, Yingchao Wang, Jingfeng Liu, High Expression Levels of CLEC4M Indicate Poor Prognosis in Patients With Hepatocellular Carcinoma. Oncol Lett. 2020;19(3):1711-1720.

(29) Y Wang#, G Wang#, X Tan#, K Ke, B Zhao, N Cheng, Y Dang, N Liao, F Wang, X Zheng, Q Li, X Liu*, J Liu*. MT1G serves as a tumor suppressor in hepatocellular carcinoma by interacting with p53. Oncogenesis, 2019, 8(12):67.

(30) Liao, N., Shi, Y., Zhang, C., Zheng, Y., Wang, Y., Zhao, B., Zeng, Y., Liu, X., and Liu, J. Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion. Stem cell research & therapy. 2019; 10:306

(31) Zhang Xiang; Wang Fei; Huang Yanbing; Ke Kun; Zhao Bixing; Chen Lihong; Liao Naishun; Wang Lei; Li Qin; Liu Xiaolong; Wang Yingchao & Liu Jingfeng. FGG promotes migration and invasion in hepatocellular carcinoma cells through activating epithelial to mesenchymal transition. Cancer Management and Research. 2019;11:1653-1665

(32) Liu Z, Wu S, Wang L, Kang S, Zhao B, He F, Liu X, Zeng Y, Liu J. Prognostic Value of MicroRNA-497 in Various Cancers: A Systematic Review and Meta-Analysis. Dis Markers. 2019, 2019: 2491291.

(33) Ke K, Chen G, Cai Z, Huang Y, Zhao B, Wang Y, Liao N, Liu X, Li Z, Liu J. Evaluation and prediction of hepatocellular carcinoma prognosis based on molecular classification. Cancer management and research, 2018, 10: 5291-5302.

(34) Yan, S., Cui, S., Ke, K., Zhao, B., Liu, X., Yue, S., & Wang, P. Hyperspectral stimulated Raman scattering microscopy unravels aberrant accumulation of saturated fat in human liver cancer. Analytical chemistry. 2018; 90: 6362−6366

(35) Wu, M., Lin, X., Tan, X., Li, J., Wei, Z., Zhang, D., Zheng, Y., Zheng, A., Zhao, B., ... & Liu, X. Photo-responsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P-gp shRNA and Doxorubicin to Optimize and Enhance Synergistic Therapy of Multidrug-resistant Cancer. ACS applied materials & interfaces. 2018, 10(23): 19416-19427.

(36) Wu, M., Li, J., Lin, X., Wei, Z., Zhang, D., Zhao, B., ... & Liu, J. Reduction/photo dual-responsive polymeric prodrug nanoparticles for programmed siRNA and doxorubicin delivery. Biomaterials science. 2018, 6(6): 1457-1468.

(37) Liao, N., Zheng, Y., Xie, H., Zhao, B., Zeng, Y., Liu, X., & Liu, J. Adipose tissue-derived stem cells ameliorate hyperglycemia, insulin resistance and liver fibrosis in the type 2 diabetic rats. Stem cell research & therapy. 2017,8(1): 286.

(38) Wei, Z., Lin, X., Wu, M., Zhao, B., Lin, R., Zhang, D. Zhang, Y., Liu, G., Liu, X. & Liu, J. Core-shell NaGdF 4@ CaCO 3 nanoparticles for enhanced magnetic resonance/ultrasonic dual-modal imaging via tumor acidic micro-enviroment triggering. Scientific Reports, 2017, 7(1): 5370.

(39)W. Chen, L. Chen, Z. Cai, D. Liang, B. Zhao, Y. Zeng, X. Liu, and J. Liu, Overexpression of annexin A4 indicates poor prognosis and promotes tumor metastasis of hepatocellular carcinoma. Tumour Biol, 2016, 37(7):9343-55

(40) W. Zhao, Y. Xu, J. Xu, D. Wu, B. Zhao, Z Yin, and X. Wang. Subsets of myeloid-derived suppressor cells in hepatocellular carcinoma express chemokines and chemokine receptors differentially. Int Immunopharmacol. 2015. 26(2): 314-21.

(41) W. Zhao, L. Zhang, Y. Xu, Z. Zhang, G. Ren, K. Tang, P. Kuang, B. Zhao, Z. Yin, and X. Wang, Hepatic stellate cells promote tumor progression by enhancement of immunosuppressive cells in an orthotopic liver tumor mouse model. Lab Invest, 2014. 94(2): 182-91.

(42) W. Wang, Y. Wang, H. Chen, Y. Xing, F. Li, Q. Zhang, B. Zhou, H. Zhang, J. Zhang, X. Bian, L. Li, Y. Liu, B. Zhao, Y. Chen, R. Wu, A. Li, L. Yao, P. Chen, Y. Zhang, X. Tian, F. Beermann, M. Wu, J. Han, P. Huang, T. Lin, and Q. Wu, Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat Chem Biol, 2014. 10(2): 133-40.

(43) R. Wang, J. He, M. Su, J. Luo, M. Xu, X. Du, H. Chen, W. Wang, Y. Wang, N. Zhang, B. Zhao, W. Zhao, Z. Shan, J. Han, C. Chang, and Q. Wu, The orphan receptor TR3 participates in angiotensin II-induced cardiac hypertrophy by controlling mTOR signalling. EMBO Mol Med, 2013. 5(1): 137-48.

(44) H. Chen, L. Li, W. Wang, X. Du, Q. Wen, J. He, B. Zhao, G. Li, W. Zhou, Y. Xia, Q. Yang, C. Hew, Y. Liou, and Q. Wu, Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis. Oncogene, 2012. 31(23): 2876-87.

(45) Y. Zhan, X. Du, H. Chen, J. Liu, B. Zhao, D. Huang, G. Li, Q. Xu, M. Zhang, B. Weimer, D. Chen, Z. Cheng, L. Zhang, Q. Li, S. Li, Z. Zheng, S. Song, Y. Huang, Z. Ye, W. Su, S. Lin, Y. Shen, and Q. Wu, Cytosporone B is an agonist for nuclear orphan receptor Nur77. Nat Chem Biol, 2008. 4(9): 548-56.

(46) H. Chen, B. Zhao, W. Zhao, L. Li, B. Zhang, and Q. Wu, Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondria. Carcinogenesis, 2008. 29(11): p. 2078-88.

(47) W. Zhao, M. Tian, B. Zhao, G. Li, B. Liu, Y. Zhan, H. Chen, and Q. Wu, Orphan receptor TR3 attenuates the p300-induced acetylation of retinoid X receptor-alpha. Mol Endocrinol, 2007. 21(12): 2877-89.

授权发明专利：

（1）发明人：刘小龙，赵必星，刘景丰，谭雄红. 一种光调控T细胞活化的表达载体、构建方法及应用. 授权号：201610404536.9, 授权日期：20200110, 专利权人: 福州市传染病医院

获奖情况

福建省科技进步一等奖，《肝癌微创与诊疗一体化技术的研究及应用》，排名第9，2022

福建省抗癌协会科技进步奖一等奖，《肝细胞癌复发转移分子标志物筛选及机制研究》，排名第1，2022

福州市最美科技工作者，2022

百千万人才工程省级人选，2021

福建省第二批“雏鹰计划”青年拔尖人才，2021

第四届福州青年科技奖，2020

福建省自然科学奖一等奖，《孤儿受体TR3通过信号转导通路抑制肿瘤细胞生长的新机制》，排名第4，2013

厦门市科技进步一等奖，《原发性肝癌的基础与临床应用研究》，排名第8，2012